The EGFR pathway is involved in the regulation of PD-L1 expression via the IL-6/JAK/STAT3 signaling pathway in EGFR-mutated non-small cell lung cancer.
Nan Zhang, Yuanyuan Zeng, Wenwen Du, Jianjie Zhu, Dan Shen, Zeyi Liu, Jian-An Huang
Author Information
Nan Zhang: Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Yuanyuan Zeng: Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Wenwen Du: Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Jianjie Zhu: Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Dan Shen: Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Zeyi Liu: Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Jian-An Huang: Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Negative regulation of the signal mediated by the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway can effectively inhibit the function of T and B cells, which play a key role in the regulation of immune response. Recently, emerging evidence has suggested that the expression of PD-L1 is related to the mutation status of the epidermal growth factor receptor (EGFR). Moreover, the activation of the EGFR signaling pathway can induce expression of PD-L1. In the present study, we demonstrated that activated EGFR can upregulate the expression of PD-L1 through the interleukin 6/Janus kinase/signal transducer and activator of transcription 3 (IL-6/JAK/STAT3) signaling pathway in non-small cell lung cancer (NSCLC) cells. Cells treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can downregulate the activation of the IL-6/JAK/STAT3 pathway, which subsequently reduces the expression of PD-L1. Furthermore, silencing of PD-L1 expression in NSCLC cells correlated with inhibition of cell proliferation and enhanced tumor cell apoptosis. In summary, our research indicates that EGFR is involved in the regulation of PD-L1 expression and cell proliferation via the IL-6/JAK/STAT3 signaling pathway in NSCLC. The present study suggests the potential of combined targeted therapy with immunotherapy in the treatment of NSCLC.
